Chemical Engineering Journal, Год журнала: 2024, Номер unknown, С. 155709 - 155709
Опубликована: Сен. 1, 2024
Язык: Английский
ACS Nano, Год журнала: 2023, Номер 17(2), С. 1583 - 1596
Опубликована: Янв. 3, 2023
The immunotherapeutic effect elicited by photodynamic therapy (PDT) is attenuated tumor defense mechanisms associated with glutamine metabolism, including the metabolic regulation of redox homeostasis and limitation immunosuppressive microenvironment (ITM). Herein, a carrier-free nanobooster C9SN dual synergistic effects was constructed self-assembly glutaminase (GLS) inhibitor compound 968 (C968) photosensitizer Chlorin e6. C968-mediated GSH deprivation through inhibiting metabolism prevented PDT-generated reactive oxygen species from being annihilated GSH, amplifying intracellular oxidative stress, which caused severe cell death also enhanced immunogenic (ICD) effect. In addition, genome-wide analysis carried out using RNA-sequencing to evaluate changes in transcriptome induced stress. Thereafter, neoantigens generated ICD promoted maturation dendritic cells, thereby recruiting activating cytotoxic T lymphocytes (CTLs). Meanwhile, remodeled ITM blocking polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, further recruited activated CTLs. Ultimately, this suppressed primary distant tumors. This "kill two birds one stone" strategy would shed light on enhancing immunogenicity alleviating immunosuppression improve PDT.
Язык: Английский
Процитировано
71
Nature Communications, Год журнала: 2023, Номер 14(1)
Опубликована: Март 25, 2023
Abstract Nanomedicine holds great promise to enhance cancer therapy. However, low active pharmaceutical ingredient (API) loading content, unpredictable drug release, and potential toxicity from excipients limit their translational capability. We herein report a full-API nanodrug composed of FDA-approved 5-aminolevulinic acid (ALA), human essential element Fe 3+ , natural bioactive compound curcumin with an ideal API content pH-responsive release profile for continuous spatiotemporal therapy achieved by multi-step tandem endogenous biosynthesis. First, ALA enzymatically converts into photosensitizer protoporphyrin IX (PpIX). Afterward, multiple downstream products including carbon monoxide (CO), 2+ biliverdin (BV), bilirubin (BR) are individually biosynthesized through the PpIX-heme-CO/Fe /BV-BR metabolic pathway, further cooperating released curcumin, ultimately eliciting mitochondria damage, membrane disruption, intracytoplasmic injury. This work not only provides paradigm exploiting diversified metabolites tumor suppression, but also presents safe efficient nanodrug, facilitating practical translation nanodrugs.
Язык: Английский
Процитировано
56
Advanced Science, Год журнала: 2024, Номер 11(15)
Опубликована: Янв. 18, 2024
Abstract The chemo‐regulation abilities of chemotherapeutic medications are appealing to address the low immunogenicity, immunosuppressive lactate microenvironment, and adaptive immune resistance colorectal cancer. In this work, proteolysis targeting chimera (PROTAC) BRD4 (dBET57) is found downregulate cancer glycolysis through transcription inhibition c‐Myc, which also inhibits expression programmed death ligand 1 (PD‐L1) reverse evasion avoid resistance. Based on this, self‐delivery nano‐PROTACs (designated as DdLD NPs) further fabricated by self‐assembly doxorubicin (DOX) dBET57 with assistance DSPE‐PEG 2000 . NPs can improve stability, intracellular delivery, tumor accumulation DOX dBET57. Meanwhile, effect efficiently destroy cells trigger a robust immunogenic cell (ICD). More importantly, effects inhibit reduce production, PD‐L1 degradation. Taking advantages chemotherapy ability, systemically activated antitumor immunity suppress primary metastatic progression without inducing any systemic side effects. Such may provide new insight for chemotherapy‐enabled immunotherapy.
Язык: Английский
Процитировано
21
Advanced Science, Год журнала: 2025, Номер unknown
Опубликована: Янв. 22, 2025
Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease that often results in irreversible joint erosion and disability. Methotrexate (MTX) the first-line drug against RA, but significant side effects of long-term administration limit its use. Therefore, new therapeutic strategies are needed for treating RA. Here, dual-targeting biomimetic carrier-free nanomaterials (BSA-MTX-CyI nanosystem, BMC) developed synergistic photo-chemotherapy Bovine serum albumin (BSA), which has high affinity with SPARC (secreted protein acidic rich cysteine) RA microenvironment, selected as hydrophilic end coupled MTX phototherapeutic agent CyI to self-assemble into BMC. In vitro vivo experiments revealed BMC accumulated significantly at site collagen antibody-induced mice could be specifically recognized taken up by folate receptors proinflammatory M1 macrophages. Upon near-infrared laser irradiation, exerted photodynamic photothermal effects, whereas not only inhibited cell proliferation also increased sensitivity reactive oxygen species, enhancing apoptotic effect induced achieving photo-chemotherapy. Moreover, induce macrophages reprogram anti-inflammatory M2 This study provides innovative approaches treatment via macrophage apoptosis re-polarization.
Язык: Английский
Процитировано
2
Advanced Healthcare Materials, Год журнала: 2022, Номер 12(4)
Опубликована: Ноя. 9, 2022
Abstract Safe and effective strategies are urgently needed to fight against the life‐threatening diseases of various cancers. However, traditional therapeutic modalities, such as radiotherapy, chemotherapy surgery, exhibit suboptimal efficacy for malignant tumors owing serious side effects, drug resistance even relapse. Phototherapies, including photodynamic therapy (PDT) photothermal (PTT), emerging localized tumor inhibition, which can produce a large amount reactive oxygen species (ROS) or elevate temperature initiate cell death by non‐invasive irradiation. In consideration poor bioavailability phototherapy agents (PTAs), lots delivery systems have been developed enhance targeted delivery. Nevertheless, carriers inevitably bring biosafety concerns on account their metabolism, degradation, accumulation. Of note, carrier‐free nanomedicine attracts great attention clinical translation with synergistic antitumor effect, is characterized high loading, simplified synthetic method good biocompatibility. this review, latest advances nanomedicines summarized, may provide new paradigm future development precision therapy.
Язык: Английский
Процитировано
49
Asian Journal of Pharmaceutical Sciences, Год журнала: 2023, Номер 18(4), С. 100829 - 100829
Опубликована: Июль 1, 2023
Current antitumor monotherapy has many limitations, highlighting the need for novel synergistic anticancer strategies. Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment. Photodynamic therapy (PDT) causes irreversible chemical damage to target lesions widely used therapy. However, PDT's effectiveness usually hindered by several obstacles, such as hypoxia, excess glutathione (GSH), tumor resistance. improves efficacy PDT increasing oxygen reactive species (ROS) or reducing GSH levels, also enhances ferroptosis induction due ROS effect microenvironment (TME). Strategies based on nanoparticles (NPs) can subtly exploit potential synergy PDT. This review explores recent advances current challenges landscape underlying mechanisms regulating PDT, well nano delivery system-mediated activity. These include polymers, biomimetic materials, metal organic frameworks (MOFs), inorganics, carrier-free NPs. Finally, we highlight future perspectives this emerging paradigm targeted cancer therapies.
Язык: Английский
Процитировано
37
Advanced Materials, Год журнала: 2023, Номер 36(3)
Опубликована: Ноя. 16, 2023
Lung cancer is the second most prevalent and leading cause of cancer-related death worldwide. Surgery, chemotherapy, molecular targeted therapy, immunotherapy, radiotherapy are currently available as treatment methods. However, drug resistance a significant factor in failure lung treatments. Novel therapeutics have been exploited to address complicated mechanisms advancement nanomedicine extremely promising terms overcoming resistance. Nanomedicine equipped with multifunctional tunable physiochemical properties alignment tumor genetic profiles can achieve precise, safe, effective while minimizing or eradicating cancer. Here, this work reviews discovered for radiotherapy, outlines novel strategies development against This focuses on engineering design, customized delivery, current challenges, clinical translation application resistant
Язык: Английский
Процитировано
36
Coordination Chemistry Reviews, Год журнала: 2023, Номер 502, С. 215600 - 215600
Опубликована: Дек. 14, 2023
Язык: Английский
Процитировано
36
Advanced Healthcare Materials, Год журнала: 2023, Номер 12(20)
Опубликована: Март 22, 2023
Traditional starvation treatment strategies, which involve glucose oxidase and drug-induced thrombi, often suffer from aggravated tumor hypoxia have failed to improve antitumor efficacy in combination with oxygen-dependent photodynamic therapy (PDT). Herein, transporter 1 inhibitor genistein (Gen) photosensitizer chlorin e6 (Ce6) are integrated construct carrier-free self-assembled nanoparticles defined as GC NPs, for therapy-amplified PDT of tumor. NPs regular morphology stability screened out by component adjustment, while the function each is preserved. On one hand, Gen released can cut off uptake inhibiting restrict growth, achieving therapy. other they able decrease amount oxygen consumed respiration amplify therapeutic effect PDT. In vitro vivo experiments verify excellent synergistic without any apparent toxicity. Moreover, fluorescence photoacoustic imaging provide guidance PDT, demonstrating enrichment efficiency NPs. It believed that this strategy holds promising clinical prospects.
Язык: Английский
Процитировано
30
Biomaterials Science, Год журнала: 2024, Номер 12(7), С. 1662 - 1692
Опубликована: Янв. 1, 2024
In this review, we have summarized the common self-assembled mechanism of NSMs-based SANDDSs. Meanwhile, potential applications for cancer treatment and future development prospects are also prospected.
Язык: Английский
Процитировано
15